The goal of this project is to determine the role of the aryl hydrocarbon hydroxylase in mouse skin tumorigenesis by benzo(a)pyrene (BP) and 7,12-dimethylbenz(a)anthracene (DMBA). Pursuant to this goal, we examined the effects of 7,8-benzoflavone (7,8-BF), 5,6-benzoflavone (5-6BF), butylated hydroxytoluene (BHT), estradiol and 1,1,1-trichloropropene 2,3-oxide (TCPO) on DMBA and BP mouse skin tumorigenesis and metabolism. The conversion of radioactive DMBA and BP by epidermis to organic solvent-soluble metabolites separated by high pressure liquid chromatography (HPLC) was used as the overall assessment of the metabolizing system. The effects of the modifying agents on the epidermally-mediated covalent binding of various polycyclic aromatic hydrocarbons (PAH) to DNA was also determined. A correlation appears to exist between the tumor initiating ability of several PAH and their ability to covalently bind to DNA in vitro using mouse epidermal homogenates and NADPH as the electrophile generating system. 7,8-BF, 5,6-BF and estradiol are potent inhibitors of the covalent binding of various PAH to DNA and the overall metabolism of BP and DMBA as revealed by HPLC. Results to date suggest that BP-7,8-diol is a proximate carcinogen of BP and BP-7,8-diol-9,10-epoxide (anti) the ultimate carcinogeneic form. Similar studies are underway for DMBA.